The purpose of this project is to study the long-term health effects of therapeutic drugs as they may relate to carcinogenicity. Cohort studies of exposed groups are conducted, as well as case-control studies of selected cancer sites which involve lifetime drug use histories. Emphasis in the past year has been on the evaluation of various types of estrogenic preparations, immunosuppressive drugs, and cancer chemotherapeutic agents. Long-term use of menopausal estrogens is related to increased risk of breast cancer. In general, oral contraceptive use is not related to increased risk of breast cancer except, perhaps, during premenopausal periods or among certain subgroups. Use of immunosuppressive drugs is associated with markedly elevated risk of non-Hodgkin's lymphoma and certain other tumors. Alkylating agents used for treatment of cancer and some non-neoplastic conditions are associated with large excess of leukemia that seem to be dose related.